Near Complete Pathologic Response to PD-1 Inhibitor and Radiotherapy in a Patient with Locally Advanced Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains deadly despite advances in systemic therapies and surgical techniques. While there is increasing utilization of immune therapies across diverse cancer types, PDAC remains generally resistant to these treatments. We report a case of locally advanced PDAC treated with preoperative radiation and anti-PD-1 immunotherapy guided by preoperative PD-L1 tumor analysis. After 4 months of preoperative therapy, the patient was submitted to resection, demonstrating a near-complete pathologic response on final tumor analysis. We will discuss the relevant literature and current state of immunotherapeutics for PDAC.

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial

“…Recently, immunotherapy is of great interest in cancer treatment. Although single-agent PD-1 inhibitor is yet to show a substantial clinical benefit in PDAC treatment, PD-1 blockade plus chemotherapy or radiotherapy provides various options for treating patients with BRPC, LAPC, 18 or metastatic PDAC. 19 In a melanoma mouse model, the combination of radiation and ICI resulted in higher response rates and improved survival.…”

“… 17 A patient with LAPC achieved near-pathologic complete response (pCR) after the combination of pembrolizumab and radiation therapy. 18 Moreover, the result of the CheckPAC clinical trial showed that SBRT plus nivolumab and ipilimumab was a promising therapy for patients with metastatic pancreatic cancer. 19 …”

Case Report: Pathologic Complete Response to Induction Therapy in a Patient With Potentially Resectable Pancreatic Cancer

“…At present, immune checkpoint inhibitors plus chemotherapy or radiotherapy have also gradually entered the public eye. The combination of chemotherapy and PD-1 antibody showed great advantages in metastatic pancreatic cancer ( 27 ), and there was a patient with LAPC who achieved near pCR after the neoadjuvant PD-1 inhibitor plus radiotherapy ( 28 ). During the 2021 meeting of the American Association for Cancer Research (AACR), professor Forde concluded the data of the phase III trial Checkmate-816 and suggested that patients in earlier-stage NSCLC who achieved a pCR with neoadjuvant chemotherapy may live longer than those who did not ( 29 ).…”

Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy

“…A case report has been published in which a patient with locally advanced PC received preoperative radiation (5 Gy × 5) and pembrolizumab (200 mg Q3W) for 4 months. After surgery, a near-complete pathological response was reported [ 51 ]. However, in a phase I trial combining pembrolizumab (200 mg Q3W, beginning 1 week before the radiation therapy) with hypofractionated radiotherapy, 4 patients with metastatic PC all displayed progressive disease (PD).…”